Because little is known about non-genetic causes of autism spectrum disorders (ASD), this proposal seeks a novel approach to advance our knowledge of the complex etiology of autism due to environmental chemical exposures from the use of common consumer products. Phthalates are selected as a chemical class of interest because they are ubiquitous in personal care products (e.g., cosmetics, fragrances, shampoos) and indoor residential environments (e.g., polyvinyl chloride (PVC) flooring and plastics, children's toys, vinyl tiles, shower curtains), have been shown to influence sex steroids critical n early brain development, and have neuro- developmental toxicity in infants and children. A recent epidemiologic study also found that having PVC flooring material (a source of airborne phthalates) in a parent's or child's room was associated with an increased risk of ASD. The overall goal of this project is to determine whether exposure to phthalates during pregnancy is associated with an increased risk of ASD. To estimate prenatal exposure to phthalates, this study will leverage existing resources from a unique longitudinal study initiated under the NIEHS-funded UC Davis Center for Children's Environmental Health known as MARBLES (Markers of Autism Risk in Babies - Learning Early Signs). MARBLES is a prospective investigation, enrolling pregnant women who already have a child with ASD and are therefore at high risk for delivering another child with autism, designed to identify causes and early markers of autism. From this study, we have available multiple urine samples collected from the mother throughout pregnancy, a key feature for improving the exposure estimates for each infant and mother due to the fact that phthalates are metabolized and excreted quickly, with elimination half-lives on the order of hours. Moreover, two hundred fifteen of the children from this pregnancy cohort will have been assessed for autism at the age of 36 months during the time of this R21, enriching the value of these prenatal biological samples. Close to one in five of the firt 147 children to reach 36 months has been confirmed with a diagnosis of ASD. Other developmental diagnoses, including adaptive function and cognitive development, are also available for these children. Therefore, multiple gestational urine samples collected from mothers and confirmed diagnoses of autism in MARBLES are invaluable resources that will enable rigorous analyses of the association between prenatal exposure to phthalates and the risk for ASD or other developmental concerns. Up to four urine samples were collected each trimester for each woman. To reduce analytical costs while maintaining some information about variability, we will analyze the first sample collected each trimester as an individual sample and pool all remaining samples for that trimester. To assess variability of maternal exposures during pregnancy, longitudinal individual urine samples collected approximately one week apart from 9 mothers will be analyzed for phthalate metabolite levels. This study will markedly advance understanding of the role of a class of endocrine disrupting compounds common in consumer products on ASD.